Unveiling the Potential of Esculetin in Cancer Models and Chemotherapy‐Induced Toxicity: Mechanistic Insights From Preclinical Evidence

Esculetin (ESC), a naturally occurring coumarin derivative identified in various medicinal plants, has garnered significant interest owing to its multifaceted pharmacological attributes. This narrative review synthesizes contemporary experimental data derived from in silico, in vitro, and in vivo investigations pertaining to ESC within cancer-associated frameworks and chemotherapy-induced organ toxicities. The extant literature indicates that ESC possesses antioxidant and anti-inflammatory properties and influences numerous signaling cascades pertinent to oxidative stress, inflammation, and oncogenic mechanisms. Within the scope of experimental investigations, ESC has been documented to amplify the anticancer efficacy of specific chemotherapeutic agents while concurrently mitigating chemotherapy-related toxicities in vital organs. The aforementioned protective effects are primarily ascribed to the preservation of redox equilibrium, attenuation of pro-inflammatory mediators, and the induction of cytoprotective pathways. Notwithstanding, clinical trials assessing ESC within these contexts are presently deficient, and discrepancies in experimental paradigms, dosing strategies, and bioavailability concerns related to formulation may impede direct translation to clinical practice. Collectively, this review elucidates ESC's structural and chemical attributes, principal pharmacological mechanisms, and its burgeoning preclinical significance in cancer models and the management of chemotherapy-induced toxicity. Subsequent research endeavors should emphasize the establishment of standardized experimental frameworks, pharmacokinetic validation, and clinical assessment to ascertain translational significance.